title: Virus immobilization on biomaterial scaffolds through biotin-avidin interaction for improving bone regeneration.
abstract: To spatially control therapeutic gene delivery for potential tissue engineering applications, a biotin-avidin interaction strategy was applied to immobilize viral vectors on biomaterial scaffolds. Both adenoviral vectors and gelatin sponges were biotinylated and avidin was applied to link them in a virus-biotin-avidin-biotin-material (VBABM) arrangement. The tethered viral particles were stably maintained within scaffolds and SEM images illustrated that viral particles were evenly distributed in three-dimensional (3D) gelatin sponges. An in vivo study demonstrated that transgene expression was restricted to the implant sites only and transduction efficiency was improved using this conjugation method. For an orthotopic bone regeneration model, adenovirus encoding BMP-2 (AdBMP2) was immobilized to gelatin sponges before implanting into critical-sized bone defects in rat calvaria. Compared to gelatin sponges with AdBMP2 loaded in a freely suspended form, the VBABM method enhanced gene transfer and bone regeneration was significantly improved. These results suggest that biotin-avidin immobilization of viral vectors to biomaterial scaffolds may be an effective strategy to facilitate tissue regeneration.
authors.affiliation: Department of Biological and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.|Department of Chemical and Materials Engineering, National Central University, Jhongli City, Taiwan.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Hu
authors.affiliation: Department of Biological and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biological and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Krebsbach
mesh_terms: D000256:Adenoviridae / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001360:Avidin / Q000378:metabolism*; D001672:Biocompatible Materials / Q000494:pharmacology*; D001710:Biotin / Q000378:metabolism*; D001861:Bone Regeneration / Q000187:drug effects*; D005780:Gelatin / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000378:metabolism; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D011916:Rats, Inbred F344; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D014018:Tissue Distribution / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D001360:Avidin; D001710:Biotin; D005780:Gelatin
keywords: biomaterial scaffolds; biotin-avidin; bone regeneration; critical-sized bone defect; gene delivery; gene therapy; tissue engineering